Summary

Most bacteria surround themselves with a tough, highly interconnected polymer called peptidoglycan. To create this wall, bacteria synthesize precursors in the cytoplasm, attach them to a lipid carrier (lipid II), transport (“flip”) this compound across the cytoplasmic membrane, and then polymerize and cross-link the monomers to the existing cell wall (1). The enzymes responsible for the cytoplasmic and extracytoplasmic steps are well known. However, hydrophilic precursors must cross the hydrophobic membrane, and the protein that conducts this critical transfer has stubbornly resisted identification. On page 220 of this issue, Sham et al. (2) present evidence that the MurJ protein of Escherichia coli performs this “flippase” function in vivo, thus solving a major puzzle in the basic pathway that synthesizes the bacterial cell wall. The new data are somewhat disconcerting, though, because in vitro experiments identified another candidate, FtsW, as the relevant flippase, with MurJ being inactive (3). We are left with the tantalizing question of how these results are to be reconciled and which protein fills this fundamental biochemical role.